HPS3 encodes a 113.7 kDa protein that functions as a component of the BLOC-2 (biogenesis of lysosome-related organelles complex-2) and is critical for early-stage melanosome biogenesis and platelet dense granule formation 1. As part of the BLOC-2 complex, HPS3 is required for proper trafficking and maturation of lysosome-related organelles (LROs), with evidence suggesting it facilitates transport of proteins like the zinc transporter TMEM163 to dense granule precursor compartments 2. Mutations in HPS3 cause Hermansky-Pudlak syndrome type 3 (HPS-3), an autosomal recessive disorder characterized by oculocutaneous albinism and bleeding diathesis due to defective platelet dense bodies and melanosomes 3. HPS-3 typically presents with mild hypopigmentation and prolonged bleeding time, with generally milder systemic manifestations compared to other HPS types, though some patients may develop enterocolitis 14. The condition has been identified across diverse populations, with notably high prevalence in Ashkenazi Jewish communities (estimated 1:200 frequency for one splice site variant) and increasing recognition in Asian and Pakistani populations, indicating broader genetic heterogeneity than initially appreciated 564. Animal models confirm HPS3's role in pigmentation, as mutations produce brown coat color phenotypes in mice and dogs 7.